The Journal of Neuroscience, October 7, 2020 • 40(41):7779 • 7779 This Week in The Journal Type I Taste Bud Cells NaCl or illuminated water over plain, non- Microglia, like other cell types, release Contribute to Salt Perception illuminated water. vesicles called exosomes, which contain pro- These results indicate that the activation teins and RNA and can be taken up by of Type I taste bud cells leads to activation Caitlin Baumer-Harrison, Martin A. other cells. Because microglial exosomes can of NaCl-responsive neurons in the rNTS contain inflammatory cytokines, Mukherjee Raymond, Thomas A. Myers, Kolbe M. and can drive drink choices in sodium- et al. hypothesized that they are responsible Sussman, Spencer T. Rynberg, et al. depleted mice. This is consistent with the for ethanol-induced neuron death. They hypothesis that ENaCs in Type I cells medi- (see pages 7795–7810) looked specifically at the effects of microglial ate appetitive responses to NaCl. Future exosomes on hypothalamic b -endorphin Taste perception is transduced by receptors work should further test this hypothesis neurons, which are lost when newborn and channels expressed in different types of by determining whether inhibiting Type I (equivalent to human third trimester) rat cells blocks physiological and behavioral taste bud cells. Sweet, umami, and bitter pups are treated with ethanol. Consistent responses to NaCl. tastes are transduced by G-protein-coupled with their hypothesis, markers of microglial receptors expressed in Type II cells, whereas exosomes were higher and their activity was sour taste depends on proton influx into greater in extracellular vesicles isolated from Type III cells. Perception of salty taste is the hypothalamus of ethanol-treated pups more complicated. Perception of aversively than those from control pups, and treating high concentrations of NaCl may depend pups with a drug that reduces exosome on the detection of anions by Type II or release attenuated loss of b -endorphin neu- Type III cells, whereas appetitive responses rons in ethanol-treated pups. appear to be mediated by amiloride-sensi- Proteomic analysis of exosomes purified tive epithelial sodium channels (ENaCs), at from cultured microglia revealed that etha- least in rodents. All three types of taste bud nol exposure increased levels of many cells express some ENaC subunits, but ami- loride-sensitive sodium currents have only immune molecules, including the comple- ment protein C1q. C1q helps initiate the been detected in cells that are most likely In mouse fungiform taste buds, GAD65 (green) is expressed in Type I cells. But because these cells have complement signaling cascade that pro- cells that express NTPDase2 (a marker of Type I cells; gray), but motes inflammation, phagocytosis, and for- generally been considered to be glia-like not in cells that express PLCb 2 (a marker of Type II cells; support cells, their role in salt perception blue) or CA4 (a marker of Type III cells; magenta), allowing mation of the membrane attack complex has been doubted. selective targeting of Type I cells. See Baumer-Harrison, (MAC), which induces cell lysis. Impor- Baumer-Harrison, Raymond, et al. ob- Raymond, et al. for details. tantly, treating rat pups with ethanol in- tained strong support for the hypothesis creased hypothalamic levels of C1q, MAC that Type I cells contribute to appetitive Microglial Exosomes Mediate proteins, and the apoptosis marker caspase- responses to NaCl by expressing chan- 3. Moreover, a drug that lowers microglia nelrhodopsin selectively in these cells. Ethanol-Induced Neuron Death levels reduced hypothalamic C1q expression Photostimulation of channelrhodopsin- in ethanol-treated rats. Finally, exosomes expressing cells on the anterior tongue Sayani Mukherjee, Miguel A. Cabrera, purified from ethanol-treated microglia evoked electrical activity in the chorda- Nadka I. Boyadjieva, Gregory Berger, increased ROS production and apoptosis in tympani nerve, which innervates taste Bénédicte Rousseau, et al. cultured hypothalamic neurons; these effects buds in that region. Tongue photostimu- – were blocked by C1q-neutralizing antibod- lation also activated gustatory neurons in (see pages 7965 7979) ies, and apoptosis was reduced by inhibiting the rostral nucleus of the solitary tract Ethanol damages the developing nervous ROS. (rNTS), where individual neurons can be system, with effects ranging from disrup- These and additional results suggest categorized based on their responses to tion of long-range communication to that ethanol exposure during develop- various tastants. Notably, rNTS gustatory microencephaly and agenesis of the corpus ment increases the release of C1q-con- neurons that showed the strongest ami- callosum. These effects stem from impair- taining exosomes from hypothalamic loride-sensitive NaCl responses also ment of neurogenesis, migration, neurite microglia. These molecules trigger forma- responded more strongly than other cells to extension, myelination, and survival, which tion of the MAC and production of ROS in photostimulation of the tongue. results partly from the activation of micro- b Remarkably, photostimulation also had -endorphin neurons, leading to apoptosis. glial immune responses and partly from Whether similar mechanisms contribute to behavioral effects in sodium-depleted mice. theproductionofreactiveoxygenspecies These mice preferred water with a low con- ethanol-induced neuronal death during the (ROS). Mukherjee et al. now report that development of other brain areas remains centration of NaCl to plain water, and they these two pathological processes are related: to be determined. similarly preferred illuminated water to immune molecules released by microglia nonilluminated water. In contrast, sodium- increase ROS production in neurons, lead- This Week in The Journal was written by Teresa Esch, Ph.D. replete mice did not show a preference for ing to neuron death. https://doi.org/10.1523/JNEUROSCI.twij.40.41.2020.